Down-regulation of tumor suppressor gene FEZ1/LZTS1 in breast carcinoma involves promoter methylation and associates with metastasis.
Down-regulation of tumor suppressor gene FEZ1/LZTS1 in breast carcinoma involves promoter methylation and associates with metastasis.
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乳腺癌中抑癌基因 FEZ1/LZTS1 的下调涉及启动子甲基化并与转移相关
DOI：
10.1007/s10549-008-0147-6
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发表时间：
2009-08
影响因子：
3.8
通讯作者：
Fu, Li
中科院分区：
文献类型：
--
作者：
Chen, Ling;Zhu, Zhengmao;Sun, Xiaodong;Dong, Xue-Yuan;Wei, Jia;Gu, Feng;Sun, Yu-Lan;Zhou, Jun;Dong, Jin-Tang;Fu, Li
FEZ 1/LZTS 1是一个位于染色体8 p22区的肿瘤抑制基因，甲基化被认为是其在肿瘤中功能丧失的机制。8 p22染色体缺失在乳腺癌中也很常见。因此，我们研究了LZTS 1是否在乳腺癌中发挥作用。我们分析了LZTS 1在RNA和蛋白质水平的表达，以及乳腺癌原发肿瘤和细胞系中启动子甲基化。我们还研究了LZTS 1表达与乳腺癌不同临床病理参数之间的关系。我们发现LZTS 1 mRNA的表达在50个原发性肿瘤中的25个（50%）和30个乳腺癌细胞系中的29个（97%）中降低。免疫组化染色显示，LZTS 1蛋白的缺失或下调72 100原发性乳腺癌（72%）。LZTS 1在RNA和蛋白水平的低表达与淋巴结转移显著相关（P< 0.05）。DNA甲基化分析显示，LZTS 1基因在乳腺癌细胞系和原发肿瘤中频繁甲基化，DNA甲基化的程度与该基因表达的降低相关。这些发现表明，LZTS 1至少通过启动子甲基化介导的转录下调在乳腺癌的发生和发展中发挥作用。
FEZ1/LZTS1 is a tumor suppressor gene located in chromosomal band 8p22, and methylation has been identified as a mechanism for its loss of function in tumors. Chromosomal deletion at 8p22 is also frequent in breast cancer. We therefore examined whether LZTS1 plays a role in breast cancer. We analyzed expression of LZTS1 at both the RNA and protein levels, and promoter methylation in a number of primary tumors and cell lines from breast cancer. We also examined the association between LZTS1 expression and different clinicopathological parameters of breast cancer. We found that the expression of LZTS1 mRNA was reduced in 25 of 50 (50%) primary tumors and 29 of 30 (97%) breast cancer cell lines. Immunohistochemical staining showed that LZTS1 protein was absent or down-regulated in 72 (72%) of 100 primary breast carcinomas. Reduced expression of LZTS1 at either the RNA or protein level was significantly correlated with lymph node metastases (P< 0.05). DNA methylation analysis revealed that the LZTS1 gene was frequently methylated in both cell lines and primary tumors from breast cancer, and the extent of DNA methylation was correlated with reduced expression of the gene. These findings suggest that LZTS1 plays a role in the development and progression of breast cancer at least through promoter methylation-mediated transcriptional downregulation.
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影响因子：
4.7
作者：
Baffa, Raffaele;Fassan, Matteo;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
影响因子：
8
作者：
Cabeza-Arvelaiz, Y;Sepulveda, JL;Chinault, AC
通讯作者：
Chinault, AC
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
11.2
作者：
Nonaka, D;Fabbri, A;Sozzi, G
通讯作者：
Sozzi, G
影响因子：
50.3
作者：
Vecchione, Andrea;Baldassarre, Gustavo;Croce, Carlo M.
通讯作者：
Croce, Carlo M.